RESUMEN
Apolipoprotein E (APOE) ε4, the strongest genetic risk for late-onset Alzheimer's disease (AD), confers greater risk in females than males. While APOE4-related modulation of structural brain integrity in AD is well documented, extant literature on sex-APOE interactions has focused on older adults. The understanding of the healthy brain as a part of the normal aging process and as distinct from explicit disease or pathology is essential before comparison can be made with pathological states. Hence, it is crucial to characterize and better understand these relationships in middle-age prior to the onset of overt clinical symptoms and advanced neurodegeneration. The present study examined the relationships between sex, APOE status, and cortical thickness in 128 healthy, cognitively unimpaired, middle-aged adults (ages 40-60, M(SD) = 49.97(6.04); 77 females). All participants underwent structural magnetic resonance imaging and were genotyped for APOE (APOE4 + = 38; APOE4- = 90). Compared to males, females had thicker superior frontal cortices bilaterally, left middle temporal cortex, and left pars triangularis. APOE4 + had thinner left rostral middle frontal gyrus compared to APOE4-. Female compared to male APOE4- had thicker left banks of the superior temporal sulcus, left caudal anterior cingulate, left superior frontal, left superior parietal, and right precentral cortices. Female compared to male APOE4 + had thicker superior frontal cortices bilaterally. Female APOE4 + had thinner left rostral anterior cingulate cortex compared to female APOE4-. Overall, APOE-related differences in cortical thickness are more pronounced in females and detectable in middle age, well before the onset of overt clinical symptoms of AD.
RESUMEN
Reversal learning is frequently used to assess components of executive function that contribute to understanding age-related cognitive differences. Reaction time (RT) is less characterized in the reversal learning literature, perhaps due to the daunting task of analyzing the entire RT distribution, but has been deemed a generally sensitive measure of cognitive aging. The current study extends our prior work to further characterize distributional properties of the reversal RT distribution and to distinguish groups of individuals with fractionated profiles of performance, which may be of clinical importance within the context of cognitive aging. Participant sample included young (n = 43) and community-dwelling, healthy, middle-aged (n = 139) adults. To explore individual differences, recursive partitioning analysis achieved a high classification rate by specifying decision tree rules that split participants into young and middle-aged groups. Mu (µ, efficient RT) was the most successful parameter in distinguishing age groups while sigma ( σ) and tau ( τ , ex-Gaussian indices of intra-individual variability) revealed more subtle individual differences. Accuracy measures did not contribute to separating the groups, suggesting that fractionated components of RT, as opposed to accuracy, can distinguish differences between young and middle-aged participants.
Asunto(s)
Envejecimiento Cognitivo/fisiología , Individualidad , Tiempo de Reacción/fisiología , Aprendizaje Inverso/fisiología , Anciano , Atención/fisiología , Función Ejecutiva , Femenino , Humanos , Vida Independiente , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Distribución Normal , Adulto JovenRESUMEN
Reversal learning assesses components of executive function important for understanding cognitive changes with age. Extant reversal learning literature has largely assessed measures of accuracy, but reaction time (RT) has not yet been well characterized, perhaps due to the daunting task of analyzing non-normal RT distributions. The current study contributes to the literature by examining distributional and theoretical aspects of the entire RT distribution in addition to accuracy. Participant sample included young (N = 43) and community-dwelling, healthy, middle-aged (N = 139) adults. Results showed a Normal-3 Mixture distribution best fits the sample as a whole, with the ex-Gaussian distribution passing visual inspection. Age related significantly to various measures of RT (p's < 0.5); older age was associated with higher both efficient and overall RT, perhaps due to a more conservative criterion of decision-making. In a generalized adaptive elastic net regression, RT explained age-related differences in performance while accuracy did not contribute. Specifically, middle-aged adults were slower in efficient RT and had increased intra-individual variability which has been previously linked to poorer frontal lobe processes and age-related cognitive decline. Overall, these findings highlight the importance of examining the entire RT distribution and measuring RT as a fractionated construct to further explain age-related differences in reversal learning, even in middle-aged individuals.
Asunto(s)
Tiempo de Reacción/fisiología , Aprendizaje Inverso/fisiología , Adolescente , Adulto , Envejecimiento/psicología , Disfunción Cognitiva/psicología , Toma de Decisiones/fisiología , Femenino , Lóbulo Frontal/fisiología , Humanos , Vida Independiente , Individualidad , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Distribución Normal , Estimulación Luminosa , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
OBJECTIVE: Cognitive impairment is a common symptom of multiple sclerosis (MS), yet treatment is currently limited. The primary goal of this pilot study was to assess the feasibility and acceptability of an at-home, five-week computerized speed of processing (SOP) training intervention for MS patients. In addition, we examined the utility of the intervention to improve speed of information processing, memory, executive function, and health-related quality of life (HRQOL). METHOD: Fifteen subjects were assigned five weeks of SOP training, two times per week, for a total of ten sessions. Subjects were trained on five computerized SOP tasks that required processing of increasingly complex visual stimuli in successively shorter presentation times. Subjects were given a neuropsychological test battery that included measures of speed of information processing, verbal memory, visual spatial memory, and executive function. Subjects were also administered patient-reported outcome (PRO) measures to assess HRQOL, depression, and work productivity. Neuropsychological and PRO batteries were completed at baseline and after five weeks. RESULTS: Eighty percent of subjects completed the five-week intervention (n = 12). Significant improvements were observed on some, but not all, measures of speed of information processing, verbal memory, and executive function. There were no significant changes in HRQOL. CONCLUSION: This pilot study supports the feasibility of an at-home SOP training intervention for individuals with MS. SOP training was associated with improvements in several cognitive domains. Larger, randomized controlled trials are warranted.
RESUMEN
BACKGROUND: Positive psychology uses targeted activities to increase the frequency and intensity of positive emotional experiences. Positive psychology interventions that increase positive constructs may facilitate adjustment and improve well-being in patients with multiple sclerosis (MS). The primary goal of this study was to assess the feasibility and acceptability of a 5-week group positive psychology intervention for patients with MS. In addition, we examined the utility of the group intervention to increase positive psychological constructs and health-related quality of life (HRQOL). METHODS: 11 patients completed 5 weeks of group positive psychology training, one time per week (session duration, 45-60 minutes). Each week, patients completed one of the following positive psychology exercises: gratitude for positive events, personal strengths, gratitude letter, enjoyable and meaningful activities, and remembering past successes. Patients completed patient-reported outcome measures, including measures of positive affect, optimism, depression, anxiety, and HRQOL, at baseline and after 5 weeks. RESULTS: All the participants completed the 5-week group positive psychology intervention, and 82% attended four or more sessions. Improvements in fatigue (vitality) and depression after the group intervention were significant (P = .016 and .049, respectively). There were no statistically significant changes in positive or negative affect, optimism, anxiety, HRQOL, or cognition. CONCLUSIONS: The 5-week group positive psychology intervention was feasible and acceptable to patients with MS. A randomized controlled trial is necessary to further explore the effectiveness of the group intervention.
RESUMEN
BACKGROUND: The recent approval of oral disease-modifying therapies (DMTs) for multiple sclerosis (MS) has provided patients with a new route of therapy administration. Little research has compared patients' experiences with and perceptions of injectable, infusion and oral MS therapies. METHODS: Three hundred fifty-seven treated MS patients enrolled in the CLIMB study completed the Treatment Satisfaction Questionnaire for Medication (TSQM). The TSQM provides information regarding perceived effectiveness, side effects, convenience and overall satisfaction. The patients were treated with either interferon beta-1a intramuscular (IFNß-1a IM) (n = 40), interferon beta-1a subcutaneous (IFNß-1a SC) (n = 45), glatiramer acetate (GA) (n = 118), natalizumab (NTZ) (n = 44), fingolimod (n = 66), or dimethyl fumarate (BG-12) (n = 44). Multivariable linear regression models were used to compare treatment satisfaction across all DMTs and between patients treated with injectable (n = 203), infusion (n = 44), and oral (n = 110) DMTs. All models were adjusted for sex, age, EDSS, and time on treatment. RESULTS: Patients taking oral DMTs reported significantly higher convenience scores compared to patients taking either injectable or infusion DMTs. The adjusted difference in the mean overall convenience score was 26.87 (95% CI: 21.4, 32.34) for the comparison of orals and injectables and 17.53 (95% CI: 11.15, 23.9) for the comparison of orals and infusion. In addition, the proportion of patients reporting a side effect was significantly lower for orals compared to injectables (adjusted OR= 0.35; 95% CI: 0.18, 0.68) and infusion compared to injectables (adjusted OR= 0.14; 95% CI: 0.05, 0.35). CONCLUSION: Patients reported treatment with the oral medications as more convenient than the injectable and infusion DMTs.